Back pain is one of the most frequently reported musculoskeletal problems in the United States. 80% of the adults will miss work at least three times in their career due to back pain. The most common factor causing low back pain is the degeneration of the disc. At the ages between 35 to 37, approximately a third of the U.S. population will have suffered from a herniated disc.
The main functions of the spine are to allow motion, transmit load and protect the neural elements. The vertebrae of the spine articulate with each other to allow motion in the frontal, sagittal and transverse planes. As the weight of the upper body increases, the vertebral bodies which are designed to sustain mainly compressive loads increase in size caudally. The intervertebral disc is a major link between the adjacent vertebrae of the spine. The intervertebral disc, the surrounding ligaments and muscles provide stability to the spine.
The intervertebral discs make up about 20-33% of the lumbar spine length. They are capable of sustaining weight and transferring the load from one vertebral body to the next, as well as maintaining a deformable space to accommodate normal spine movement. Each disc consists of a gelatinous nucleus pulposus surrounded by a laminated, fibrous annulus fibrosus, situated between the end plates of the vertebrae above and below.
The nucleus pulposus contains collagen fibrils and water-binding glycosaminoglycans. At birth, the nucleus pulposus contains 88% water, however, this percentage decreases with age. This water loss decreases its ability to withstand stress. The annulus fibrosus consists of fibrocartilaginous tissue and fibrous protein. The collagen fibers are arranged in between 10 to 20 lamellae which form concentric rings around the nucleus pulposus. The collagen fibers within each lamella are parallel to each other and runs at an angle of approximately 60 degrees from vertical. The direction of the inclination alternates with each lamellae. This crisscross arrangement enables the annulus fibrosus to withstand torsional and bending loads. The end-plates are composed of hyaline cartilage, and are directly connected to the lamellae which form the inner one-third of the annulus.
When under compressive loads, the nucleus pulposus flattens and bulges out radially. The annulus fibrosus stretches, resisting the stress. The end-plates of the vertebral body also resist the ability of the nucleus pulposus to deform. Thus, pressure is applied against the annulus and end-plate, transmitting the compressive loads to the vertebral body. When tensile forces are applied, the disc is raised to a certain height straining the collagen fibers in the annulus. At bending, one side of the disc is in tension while the other side is in compression. The annulus of the compressed side bulges out.
When the disc is subjected to torsion, there are shear stresses which vary proportionally to the distance from the axis of rotation, in the horizontal and axial plane. The layer of fibers oriented in the angle of motion is in tension while the fibers in the preceding or succeeding layer are relaxed. Similarly in sliding, the fibers oriented in the sliding direction are in tension while the fibers in the other layers relax.
Repeated rotational loading initiates circumferential tears in the annulus fibrosus, which gradually form radial tears into the nucleus pulposus until the nucleus degrades within the disc. In addition to the water loss which occurs with age, more water is also lost due to nucleus rupture, thereby reducing its ability to resist compressive loads. As such, the annulus bulges. As the severity of the tear increases, much of the contents of the disc is lost, leaving a thin space of fibrous tissue. This condition is called disc resorption.
Increasing disc collapse can cause facet subluxation and stenosis of the intervertebral foramen. Subsequently, the degenerative process involves the facet joints equally. As the annulus bulges out posteriorly into the spinal canal, the nerve root may be compressed causing sciatica. Pain is felt from the lower back to the buttocks and the leg. Following the rupture of the disc, excessive motions such as excessive extension or flexion can occur, resulting in spine segmental instability. The spine is thus more vulnerable to trauma. Herniation can occur due to disc degeneration or excessive load factors, especially compression. Pain may result due to nerve root compression caused by protrusions.
The unstable phase of the degeneration progress allowing excessive movement may result in degenerative spondylolisthesis, which is a breakdown of posterior joints. The nerve is trapped between the inferior articular facet of the vertebrae above and the body of that below. Thus, sliding of a vertebral body on one another damages the posterior joints due to fatigue and applies traction on the nerve root causing pain.
Surgical treatments for herniated disc include laminectomy, spinal fusion and disc replacement with protheses.
At this time, 150,000 spinal fusion procedures are performed per year in the U.S. alone, and the numbers are growing exponentially. However, the results of spinal fusions are very varied. Some of the effects include non-unions, slow rate of fusion even with autografts, and significant frequency of morbidity at the graft donor site. In addition, even if the fusion is successful, joint motion is totally eliminated. Adverse effects of spinal fusions have also been reported on adjacent unfused segments such as disc degeneration, herniation, instability spondylolysis and facet joint arthritis. A long-term follow-up of lower lumbar fusions in patients from 21 to 52 years of age found that 44% of patients with spinal fusions were currently still experiencing low-back pain and 57% had back pain within the previous year. 53% of the patients tracked were on medication, 5% had late sequela secondary surgery, 15% had a repeat lumbar surgery, 42% had symptoms of spinal stenosis, and 45% had instability proximal to their fusion. This clinical data shows that significant long-term limitations are associated with spinal fusion.
An alternative to spinal fusion is the use of an intervertebral disc prosthesis. Ideally, a successful disc prosthesis will simulate the function of a normal disc. The disc replacement must be capable of sustaining weight and transferring load from one vertebral body to the next. It should be robust enough not to be injured during movement and should maintain a deformable space between the vertebral body to accommodate movement.
Disc protheses should last for the lifetime of the patient, should be able to be contained in the normal intervertebral disc space, should have sufficient mechanical properties for normal body function, should be able to be fixed to the vertebrae adjacent to the disc, should be possible to implant, should not cause any damage should the disc fail, and should be biocompatible.
There are at least 56 artificial disc designs which have been patented or identified as being investigated, McMillin C. R. and Steffee A. D., 20th Annual Meeting of the Society for Biomaterials (abstract) (1994), although not all these devices have actually been made or tested. They can be divided into two main categories. Lee et al., Spine, Vol. 16, 253-255 (1991). A first class includes devices for nucleus pulposus replacements which includes metal ball bearing, a silicone rubber nucleus, and a silicone fluid filled plastic tube. Devices for total or subtotal replacement of the disc have also been proposed such as a spring system, low-friction sliding surfaces, a fluid filled chamber, elastic disc prosthesis and elastic disc encased in a rigid column.
An example of total disc replacement is described by Urbaniak et al., Bio. J. Med. Mater. Res. Sym., Vol. 4, 165-186 (1973) who developed and tested, using chimpanzees, an intervertebral disc device made of a central silicone layer sandwiched between two layers of Dacron embedded in the silicone. The open-mesh Dacron was chosen to allow tissue ingrowth for fixation to the adjacent vertebrae. While spinal mobility was restored and the device tolerated by the host, due to inexact fit of the device, bone resorption and reactive bone formation were observable. Loose fibrous tissue also indicated possible movement of the device.
Hou et al., Chinese Medical Journal, Vol. 104(5), 381-386 (1991), developed a disc implant made of silicone rubber which restored normal disc function. However, the presence of fibrous tissue surrounding the implant indicated possible movement of the device.
The SB Charite intervertebral disc endoprosthesis, White and Panjabi, Clinical biomechanics of the lumbar spine, Churchill Livingstone, London (1989), which has been tested clinically, is fabricated from a biconvex polyethylene core sandwiched between two concave-molded titanium end-plates. However, the endoprosthesis shows insufficient mechanical performance and unlikely long-term bone fixation to the device.
Two types of disc prostheses were developed and evaluated by Lee et al., 35th Annual Meeting of the Orthopaedic Research Society, Las Vegas, Nev., February 6-9 (1989): Dacron fiber-reinforced polyurethane elastomer (reinforcement located for the annulus section), and a prosthesis made from thermoplastic polymer which is increasingly rigid moving from the nucleus out to the end-plates. Yet another design is made of cobalt-chromium-molybdenum (Co--Cr--Mo) alloy by Hedman et al., Spine, Vol. 16, 256-60 (1991).
U.S. Pat. No. 4,911,718 (Lee et al.), U.S. Pat. No. 5,002,576 (Fuhrmann et al.), U.S. Pat. No. 4,911,718 (Lee et al.) and U.S. Pat. No. 5,458,642 (Beer et al.) also teach permanent intervertebral disc endoprostheses for total disc replacement.
All of the foregoing intervertebral disc prostheses, however, merely replace all or a part of the disc with synthetic materials which must remain in place ad infinitum. These prostheses are generally permanent implants which require observation of long term biologic responses throughout the life of the prothesis. Furthermore, discs that are not comprised of biocompatible material may be rejected by the patient.
Procedures by which the tissues of the intervertebral disc are made to reform or replace the degenerated tissue of the intervertebral disc would be highly desirable and a significant improvement over the current state of the art which presently use such permanent implants. Although efforts in tissue-engineering have been reported, no one has, until now, accomplished reformation of intervertebral disc tissue.
Repair of skin tissue has been achieved. For instance, skin deficiencies which arise in severely burnt patients or in decubitus wounds of diabetic patients have been so treated. Sabolinski, Biomaterials, Vol. 17, 311-320 (1996). Cells are seeded onto templates of either resorbable or non-resorbable material. Once tissue begins to form the templates are dressed onto the site in need of treatment. Tissue engineering of the skin, however, is significantly different from tissue engineering of the intervertebral disc because tissue compositions differ significantly. In addition, the mechanical requirements of engineered skin tissue are significantly different from those of intervertebral disc tissue.
Some intervertebral disc prostheses provide for regrowth of the intervertebral disc and concurrent resorption of the prothesis. For example, U.S. Pat. Nos. 4,772,287 and 4,904,260 (Ray et al.) teach prosthetic discs having an outer layer of strong, inert fibers intermingled with bioresorbable materials which attract tissue ingrowth. However, this prosthesis is purely a synthetic material at the time of implantation and does not include any cells or developing tissue. In addition, it provides only partial resorption and the problems associated with permanent implants remain.
U.S. Pat. Nos. 5,108,438 and 5,258,043 (Stone) teach a porous matrix of biocompatible and bioresorbable fibers which may be interspersed with glycosaminoglycan molecules. The matrix serves as a scaffold for regenerating disc tissue and replaces both the annulus fibrosus and nucleus pulposus. However, replacement of this much tissue is a relatively invasive procedure which requires lengthy recovery time. Furthermore, these matrices do not use any cells to stimulate tissue recovery nor is there any incipient tissue formation in this device at the time of implantation.
Various materials have been seeded with cells in order to facilitate cell function including proliferation and extracellular matrix synthesis. For instance, El-Ghannam, et al., Journal of Biomedical Materials Research, Vol. 29, 359-370 (1974), teaches in vitro synthesis of bone-like tissue using bioactive glass templates. Schepers, et al., J. Oral Rehab., Vol. 18, 439-452 (1991), analyzed the use of bioactive glass as fillers for bone lesions. Also, porous polymeric matrices have been used. The polymers include poly(lactic acid), poly(glycolic acid) and their co-polymers. However, these polymers have not been taught to be appropriate substrates for intervertebral disc cells which until now have not been used to seed implants of any sort.
Ideally, intervertebral disc treatment would guide and possibly stimulate the reformation of the tissue of affected intervertebral disc, especially nucleus pulposus and annulus fibrosus tissue. It could also biodegrade while allowing concurrent nucleus pulposus and annulus fibrosus tissue ingrowth, thereby providing for disc regeneration. Such an intervertebral disc material which is biodegradable while still satisfying the mechanical requirements of an intervertebral disc, has not been available until now.